Epilepsy Flashcards
Epilepsy: Pregnancy and Breastfeeding
Epilepsy: pregnancy and breast feeding
The risks of uncontrolled epilepsy during pregnancy generally outweigh the risks of medication to the fetus. All women thinking about becoming pregnant should be advised to take folic acid 5mg per day well before pregnancy to minimise the risk of neural tube defects. Around 1-2% of newborns born to non-epileptic mothers have congenital defects. This rises to 3-4% if the mother takes antiepileptic medication.
Other points
- aim for mono therapy
- there is no indication to monitor antiepileptic drug levels
- sodium valproate: associated with neural tube defects
- carbamazepine: often considered the least teratogenic of the older anti epileptics
- phenytoin: associated with cleft palate
- lamotrigine: studies to date suggest the rate of congenital malformations may be low. The dose of lamotrigine may need to be increased in pregnancy
Breast feeding is generally considered safe for mothers taking antiepileptics with the possible exception of the barbiturates
It is advised that pregnant women taking phenytoin are given vitamin K in the last month of pregnancy to prevent clotting disorders in the newborn
Status Epilepticus
Status epilepticus
This is a medical emergency. The priority is termination of seizure activity, which if prolonged will lead to irreversible brain damage. First-line drugs are benzodiazepines such as diazepam or lorazepam. If ineffective within 10 minutes it is appropriate to start a second-line agent such as phenytoin, sodium valproate, levetiracetam, or phenobarbital. If no response within 30 minutes from onset, then the best way to achieve rapid control of seizure activity is induction of general anaesthesia
Family planning in Epilepsy
Family planning and pregnancy can be a time of anxiety for a woman with epilepsy and their families. An increase in seizure frequency is reported to occur in 14-32 % of pregnant women with epilepsy. Seizures can be harmful to both mother and fetus. The risk of major congenital malformation in a child born to a woman taking antiepileptic drugs is increased compared to the general population (roughly from 1-3 / 100 live births, to 2-5 / 100 live births).
There are no randomised controlled trials of antiepileptic drugs in pregnancy, with data based on observational studies only. From these trials, general conclusions have been reached:
Valproate has the highest risk of teratogenicity, with topiramate having a moderate risk
Lamotrigine, levetiracetam and carbamazepine are considered to have the lowest risk of teratogenicity, although carbamazepine is often poorly tolerated
Treatment with more than one drug (polytherapy) increases the risk of teratogenicity compared to monotherapy
Most appropriate strategy is to find monotherapy (can be dual therapy but mono preferred) with a drug she is known have efficacy and be tolerable to with cessation of anything potentially teratogenic. The risk of adjustments to her medication regime reducing seizure control should be discussed with the patient, including the risk of sudden unexpected death in epilepsy.
Prescribing in patients with Epilepsy
The following drugs may worsen seizure control in patients with epilepsy:
alcohol, cocaine, amphetamines
quinolone Abx: ciprofloxacin, levofloxacin
aminophylline, theophylline
bupropion
methylphenidate (used in ADHD)
mefenamic acid
Some medications such as benzodiazepines, baclofen and hydroxyzine may provoke seizures whilst they are being withdrawn.
Other medications may worsen seizure control by interfering with the metabolism of anti-epileptic drugs (i.e. P450 inducers/inhibitors).
Analgesics that are known to induce seizures or worsen seizure control include fentanyl, mefenamic acid, and tramadol (among others). Other drugs that are known to induce seizures include amitriptyline, aminophylline, isotretinoin and haloperidol.
Anti epileptic medication and contraception
It is important to be aware of the interaction between contraception and antiepileptic medication; contraceptive failure, teratogenicity and reduced seizure control are potential effects.
P450 enzyme inducers will decrease the drug level and therefore increase the failure rate of oestrogen and progesterone containing contraceptives. Carbamazepine Oxcarbazepine Phenytoin Phenobarbitone Primidone Topiramate
Antiepilpetics - Example Question
A 17 year old girl is brought to the Emergency Department following a prolonged seizure lasting seven minutes. She is known to suffer from epilepsy and has been stable on lamotrigine for eight years, having on average only one generalised tonic clonic seizure every eight months. Her mother describes an increase in her seizure frequency over the last four weeks; she has has three generalised tonic-clonic seizures during this period, each lasting around three minutes. There have been no changes to stress levels, sleep pattern or diet. She confirms she has however started a new medication for dysmenorrhoea. Which is the most likely to explain this increase in frequency?
Medroxyprogesterone (Depo-Provera) > Mefenamic acid Ibuprofen Aspirin Naproxen
Taking a full medication history is an essential aspect of any history; it can be particularly important in epilepsy, not only to gauge medication compliance and anti-epileptic therapy, but to determine any precipitating factors.
Analgesics that are known to induce seizures or worsen seizure control include fentanyl, mefenamic acid, and tramadol (among others). Other drugs that are known to induce seizures include amitriptyline, aminophylline, isotretinoin and haloperidol.
MERRF syndrome: myoclonus epilepsy with ragged-red fibres
= a mitochondrial DNA disorder diagnosed by ragged red fibres on muscle biopsy.
Presentation:
Cognitive impairment developing after a period of normal development, seizures, myoclonic jerks, Wolff-Parkinson White syndrome and worsening vision (consistent with optic atrophy).
Example:
A 14 year old boy presents his third generalised seizure over the past 72 hours, despite recently being started on sodium valproate by a neurologist for recurrent seizures 6 weeks ago, with worsening vision at night and hearing loss bilaterally. The patient has a number of myoclonic jerks as you arrive. On examination, his heart sounds are unremarkable but you notice a tachycardia at 140 and regular. The ECG shows WPW.
The patient is uncooperative to further neurological examination but you notice sluggishly reactive pupils of equal size. His mother reports that he has been educated in a special needs school for the past 5 years but had been attending the local primary school until aged 9, when he dropped further behind than his peers. Which investigation produces the underlying diagnosis?
Status Epilepticus
This is a medical emergency. The priority is termination of seizure activity, which if prolonged will lead to irreversible brain damage. First-line drugs are benzodiazepines such as diazepam or lorazepam. If ineffective within 10 minutes it is appropriate to start a second-line agent such as phenytoin, sodium valproate, levetiracetam, or phenobarbital. If no response within 30 minutes from onset, then the best way to achieve rapid control of seizure activity is induction of general anaesthesia.
Example Question:
A 23 year-old student with epilepsy presents with generalised tonic-clonic status epilepticus. He is already taking phenytoin. Despite intravenous administration of diazepam and then phenobarbital, he is still fitting after 30 minutes.
What is the best course of action?
Check phenytoin levels and reload if necessary Send urine for toxicology Organise brain imaging Obtain an electroencephalogram (EEG) > Induction of general anaesthesia with thiopentone
Absence Seizures
Absence seizures (petit mal) are a form of generalised epilepsy that is mostly seen in children. The typical age of onset of 3-10 years old and girls are affected twice as commonly as boys
Features
absences last a few seconds and are associated with a quick recovery
seizures may be provoked by hyperventilation or stress
the child is usually unaware of the seizure
they may occur many times a day
EEG: bilateral, symmetrical 3Hz spike and wave pattern
Management
sodium valproate and ethosuximide are first-line treatment
good prognosis - 90-95% become seizure free in adolescence
Absence Seizures - Which anti-epileptic is contraindicated?
CARBEMAZEPINE
Classically, carbamazepine can aggravate juvenile myoclonic epilepsy and absence seizures. In general, carbamazepine should always be avoided in patients where the type of seizure is uncertain. It is otherwise a useful AED in the treatment of partial or secondary generalised seizures.
Pregnancy and Lamotrigdine - Example Question
A 27-year-old caucasian woman is 28 weeks pregnant. She has been epileptic since the age of 7 and takes lamotrigine, which she has continued throughout the pregnancy. She has not had a seizure for 2 years. What must you consider in pregnant patients taking lamotrigine?
> Serum lamotrigine levels fall in the second trimester She must not breastfeed while taking lamotrigine She should be advised to stop lamotrigine Folic acid 400mcg should be taken throughout pregnancy It is protein bound and therefore drug levels increase in pregnancy
Due to the increased plasma volume and enhanced renal/hepatic drug clearance, lamotrigine levels decrease in the second trimester of pregnancy. It may be necessary to increase the dose of lamotrigine at this time (normally increased two or three fold). A baseline serum drug level is useful to establish compliance and inform future changes in drug doses.
Breastfeeding is not contraindicated in women taking lamotrigine. However, the infant should be monitored for signs of accumulation such as a rash or drowsiness.
Patients should not stop their anti-epileptic medications unless a joint decision has been made in conjunction with an obstetrician/obstetric physician doctor. If a patient has been seizure-free for >2 years and is on dual therapy then it may be beneficial to reduce/stop one of the medications.
Patients on anti-epileptic medications should take folic acid 5mg throughout pregnancy.
Lamotrigine has low levels of protein binding and therefore is not affected by the decreased serum protein levels in pregnancy.
Initial Anti-epileptic Choice in woman of child-bearing age - Example Question
A young woman (aged 23) attends the first seizure clinic following a tonic-clonic seizure 10 days previously. She is diagnosed with epilepsy based on clinical history from her boyfriend who witnessed the full seizure. On questioning she is keen to have a family but not in the immediate future.
What is the most appropriate anti-epileptic?
Sodium valproate Phenytoin Carbamazepine Levetiracetam > Lamotrigine
ALL anti-epileptics have the potential to cause neural-tube defects. It is widely considered that carbamazepine and lamotrigine are the safest to use in pregnancy. The risk of neural-tube defects can be further reduced by planning pregnancy and the use of folic acid.
Both lamotrigine and carbamazepine are considered ‘safest’ in pregnancy, especially when compared to valproate and phenytoin. In this case of a primary generalised seizure lamotrigine is the most appropriate choice as a first line agent, with carbamzepine being a second line drug in this presentation.
Epilepsy - First Seizure Mx:
Most neurologists now start antiepileptics following a second epileptic seizure. NICE guidelines suggest starting antiepileptics after the first seizure if any of the following are present:
- the patient has a neurological deficit
- brain imaging shows a structural abnormality
- the EEG shows unequivocal epileptic activity
- the patient or their family or carers consider the risk of having a further seizure unacceptable
Example Question:
An 18 year old man presents to your follow up clinic after a first episode of generalised tonic-clonic seizures, witnessed by his mother lasting for 4 minutes, involving all 4 limbs, before spontaneously terminating. He was initially referred to a first fit clinic and underwent an EEG and MRI, neither of which demonstrated any significant abnormalities. He has now returned to discuss his results and further treatment. The patient and his family realise that there are many ways to manage seizures and are happy to take your recommendation. What is you treatment?
> No treatment Sodium valproate Lamotrigine Levetirecetam Carbamazepine
Treatment is not usually recommended after a single seizure, as this may have been a provoked seizure instead of the first presentation of epilepsy. One prospective but metholodogically flawed prospective study demonstrated a 14% risk of seizure recurrent after a single, unprovoked seizure at 1 year1. However, the risks significant increase after a patient has had two seizures, rising to 73% recurrent rate at 4 years2. It is therefore accepted that antiepileptic treatments should only be commenced after 2 seizures, except if the risks of a further seizure is unacceptable to the patient, an underlying structural defect is proven to be the likely cause of the seizure or if the EEG demonstrated epileptiform activity.
Epilepsy - First Line Mx: Choice of Anti-Epileptic
Sodium valproate is considered the first line treatment for patients with generalised seizures with carbamazepine used for partial seizures
Generalised tonic-clonic seizures
sodium valproate
second line: lamotrigine, carbamazepine
Absence seizures* (Petit mal)
sodium valproate or ethosuximide
sodium valproate particularly effective if co-existent tonic-clonic seizures in primary generalised epilepsy
Myoclonic seizures
sodium valproate
second line: clonazepam, lamotrigine
Partial seizures
carbamazepine or lamotrigine
second line: sodium valproate
*carbamazepine may actually exacerbate absence seizure
Levetiracetam
It is important to recognise and know something about levetiracetam as it is increasingly becoming a favourite for neurologists to use these days, not least because of its favourable adverse effects profile (wherein it hardly has any compared to many others), but also its ease of use given that you do not need to monitor levels, and its oral and IV bioavailability are the same (useful in nil by mouth patients). It is also recently more affordable having now lost its patent. The one thing to watch out (and ensure you warn patients about) with levetiracetam is behavioural abnormalities and psychotic symptoms. These range from irritability to frank aggression. If there is a background of psychotic symptoms you may wish to avoid levetiracetam. It is something not to miss in the drug history of an epileptic patient who presents to the acute take with a change in behaviour.
